Uncoupling protein is a peptide that is believed to be located in the mitochondria of mammalian brown adipose tissue (BAT) and, more recently, in other tissues such as murine muscle (MUCP2, Ricquier et al., Genbank accessionnumber:U69135). It is predominant in rodent fat deposits (Saverio et al., The Endocrinology Journal, 138 (2), 1997), and leads to a dissipation of the proton gradient across the inner membrane of the mitochondrion. This, in turn, uncouples the oxidative phosphorylation chain, and "decontrols" the process. The roles played by uncoupling protein (UCP) are that of an important factor in the thermogenesis of tissue, and of energy expenditure as a whole. Therefore, this could be used to combat obesity and body weight -associated disorder by increasing BAT oxidation.
Human UCP is found predominantly in brown adipocytes (Cassard et al., Journal of Cell Biochemistry, 43, 1990). UCP mRNA is expressed at a higher rate when .beta.-3 adrenoreceptors are agonized by, for example BRL 37344 (Chengjun et al., The Endocrinology Journal, 138(2), 1997), which suggests a use for the protein in controlling insulin dependent diabetes. Patent application no WO96/05861 disloses a gene sequence with high homology to MUCP2. Human UCP2 is described by Fleury et al. in Nature Genetics, 1997, 15, 269. More recently, a further member of the family, Uncoupling protein-3, has been described (Boss O et al., FEBS Lett, May 12, 1997, 408(1), 39-42; Vidal-Puig A et al., Biochem Biophys Rs Commun, Jun. 9, 1997, 235(1), 79-82). These papers were however published after the two priority dates (Mar. 5, 1997 and Mar. 18, 1997) claimed in the present application.
There is a need for identification and characterization of further members of the Uncoupling proteins family which can play a role in preventing, ameliorating or correcting dysfunction or diseases, including, but not limited to, obesity, diabetes, hyperlipidaemia and body weight disorder.